I. Field of the Invention
Embodiments of this invention are directed generally to biology, medicine, and cardiology. In particular aspects, the invention is related to combination therapy for treating cardiac and cardiovascular disorders and conditions, such as reperfusion injury.
II. Background
Currently, there are 5 million American with congestive heart failure, with nearly 500,000 new cases being diagnosed every year. Because of the high total direct costs of care for heart failure, estimated at $10 billion to $38 billion per year, the Centers for Medicare and Medicaid Services targeted heart failure as the disease most worthy of cost-effective management. Improvement in heart failure treatment in terms of innovative pharmacological strategies are urgently needed in this heart failure epidemic era.
In addition, acute myocardial infarction (MI) is the leading killer in the Unite States accounting for 54% mortality of total cardiovascular disease-related death (2004 NHLBI Chartbook). Although reperfusion therapy during acute MI with percutaneous coronary intervention (PCI) or thrombolysis salvages myocardium that would ultimately die without reperfusion, rapidly restoring blood flow to myocardium can also cause lethal injury to vulnerable myocardial cells (i.e., reperfusion injury). The restoration of blood flow can lethally compromise oxygen-deprived cells. Reperfusion injury may offset the optimal salvage of myocardium achieved by PCI and/or thrombolysis. Over the last 20 years extensive research efforts have been devoted to develop therapeutic strategies to prevent reperfusion injury.
Intravenous infusion of synthetic calcitonin-gene related peptide has been shown to improve cardiac hemodynamic performance and improve heart failure (a chronic condition as contrasted to acute MI) symptoms in patients with advanced heart failure. Additionally, adrenomedullin has also been shown to augment cardiac performance and improve clinical symptoms in heart failure patients (Nagaya, 2000). However, i.v. infusion of synthetic CGRP or adrenomedullin have not been approved by FDA for clinical use.
There is a need for additional compositions and methods for the treatment of cardiac and cardiovascular disorders, reperfusion injury, and post-ischemia conditioning.